1. Field of the Invention
The present invention is directed to a process for producing monosubstituted cyclodextrins, a process for increasing the solubility thereof and compositions containing the same.
2. Description of Related Art
In many applications of cyclodextrins the use of mixtures of derivatives are preferred to the use of a chemically individual compound. The previous patent application by J. Pitha and B. Lindberg, described the use of controlled basic conditions to provide such mixtures but substituted in a side-specific manner. The background section of the former application describing the previous art is to be considered common with the present report. The mentioned controlled basic conditions have presently been used to prepare monosubstituted cyclodextrins. In these preparations the ability of cyclodextrins (in this context called host compounds) to form crystalline complexes of low solubility with a variety of organic compounds (called guest compounds) was used. This ability is well-known, e.g., F. Cramer and F. R. Henglein (Chem. Berichte 90, 2561-1571, 1957) described fifty examples of complexes of parent cyclodextrins; nevertheless, this ability has not been used to fractionate cyclodextrin derivatives.
The techniques used to replace hydroxy groups with amino groups using heterogenous catalysts were the subject of many publications and patents, and amino derivatives of polyethylene and propylene glycols are currently made by a similar process on an industrial scale (E. L. Yeakey, U.S. Pat. No. 3,654,370). A similar replacement has not been attempted on cyclodextrins. The only instance when cyclodextrins were treated with heterogenous catalyst (Raney nickel) was in the preparation of cyclodextrins deuterated on carbon atoms (Y. Kuroda, M. Yamada, and I. Tabushi, Tetrahedron Lett. 29, 4467-4470, 1988). Cyclodextrin sulfates have been known for a number of years (e.g., J. Hamuro and M. Akiyama, Japan Kokai 75 36 422, 1975, Chem. Abst. 83, 29026v, 1977; S. Bernstein, J. P. Joseph, and V. Nair, U.S. Pat. No. 4,020,160, 1977) and in all their preparations principally similar methods have been used. The only factor requiring investigation in the preparation of hydroxypropylcyclodextrin sulfates was to find whether the presence of the substituent in question would not lead to a partial decomposition which would lead to an unremovable and unacceptable coloration in the products.